A CONTROLLED-STUDY OF DANAZOL FOR THE TREATMENT OF KARYOTYPICALLY NORMAL SPONTANEOUS PREMATURE OVARIAN FAILURE

Objective: To determine if the immunomodulatory and gonadotropin-suppr essing properties of danazol would improve follicle function or ovulat ion rates in patients with karyotypically normal spontaneous premature ovarian failure. Design: Prospective, double-blind, crossover trial. Setting: Tertiary care research institution. Interventions: Two interv ention phases lasting 4 months each: one phase during which patients r eceived a standardized estrogen and progestin replacement regimen and one phase during which each patient received a twice daily 400 mg oral dose of danazol. Patients: Fifty-two patients with karyotypically nor mal spontaneous premature ovarian failure ranging in age from 21 to 39 years. Main Outcome Measures: We measured serum E(2) and P levels wee kly during the 2 months after each intervention. We defined a serum E( 2) > 50 pg/mL (184 pmol/L) as evidence of ovarian follicle function an d a P > 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation. Results: Of the 46 patients who completed the study, danazol did not significantly enhance ovarian follicle function or the chance of ovulation. Eight p atients ovulated after danazol and four patients ovulated after estrog en and progestin. The power to detect a 30% and a 5% ovulation success rate with therapy was 0.80 and 0.90, respectively. Overall, 30 of 46 women (65%) demonstrated ovarian follicle function and 10 women (21%) ovulated. Conclusion: We were unable to demonstrate a statistically si gnificant benefit from the immuno-modulatory and gonadotropin-suppress ing effects of danazol in patients with karyotypically normal spontane ous premature ovarian failure. These patients often have spontaneous r emission. Thus, controlled studies are required to determine the effec tiveness of treatments for this condition.